WHITE PAPER
Long Chain Omega-3 Fatty Acids
In Human Health
The Vital Roles of Eicosapentaenoic,
Docosahexaenoic and Alpha-Linolenic Acids
(EPA, DHA, and ALA)
A VITAL CHOICE WHITE PAPER
Long Chain Omega-3 Fatty Acids
In Human Health
(Last updated October 25, 2007)
Click underlined topics to jump down to each
Contents
 Introduction
 Essential Fatty Acid Overview
o Cardiovascular (Heart) Health
o American Heart Association Recommendations for Omega-3 Intake
o Alzheimer’s Disease and other Dementias
o Mental Health
o Child Development
o Attention-Deficit Disorders and Social/Cognitive Development
o Diabetes
o Inflammatory Diseases (rheumatoid arthritis, IBS/Crohn’s, asthma, etc.)
o Cancer
 Safety Considerations
 Intake Recommendations
 Best Sources
 Further Reading
 References
Introduction
The overwhelming majority of scientific evidence indicates that people whose diets
contain ample amounts of long-chain “marine” omega-3 fatty acids (EPA and DHA) –
whether obtained from fish or fish oil capsules – enjoy reduced risks of heart disease,
sudden cardiac death, stroke, depression, anxiety, and macular degeneration.
However, omega-3s of all kinds (fish-derived and plant-derived) have become very
scarce in the diets consumed in America and many other countries.
In addition, the proportion of omega-3s to omega-6 fatty acids in modern diets is
radically lower than it was over millions of years of evolutionary history.
This White Paper presents a summary of the scientific evidence concerning the effects
of omega-3 fatty acids and the omega-3/omega-6 intake ratio on heart health, mental
health, child development, cancer, diabetes, inflammation, and other health concerns.
Essential fatty acids (EFAs) in brief
To survive and thrive, humans need to consume two kinds of nutritionally essential fatty
acids: omega-3 and omega-6.
While these fatty acids constitute essential structural and functional components of our
cells, and regulate many critical aspects of metabolism and immunity, they cannot be
synthesized in our bodies and must be obtained from our diets.
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Omega-3 EFAs
Omega-3 EFAs are found in two places:
 Leafy green vegetables and certain seeds and oils.
 Fish, shellfish, zooplankton, and aquatic plants (algae, plankton, seaweed).
Only fish, shellfish, zooplankton, and aquatic plants contain the long-chain or “marine”
omega-3 fatty acids the human body actually uses:

Omega-3 DHA is an essential component of all cell membranes. DHA is also the
dominant fatty acid in human brains, and is essential to proper brain and eye
functioning and to regulation of metabolic rate. (DHA stands for docosahexaenoic
acid.)

Omega-3 EPA is found in all cell membranes, and is needed to make critical
inflammation-moderating messenger chemicals called eicosanoids. (EPA stands
for eicosapentaenoic acid.)
Plant foods contain a “short-chain” omega-3 fatty acid called alpha-linolenic acid (ALA),
whose primary purpose in the body is to provide the raw material with which to make the
long-chain, “marine” omega-3s essential to good health.
When you see reports about the benefits of omega-3s, these almost invariably refer to
the results of studies using one or both of the long-chain marine omega-3s (DHA and
EPA).
Researchers employ the long-chain “marine” omega-3s in biomedical studies because
these omega-3s yield much stronger effects in much smaller amounts, compared with
plant-derived omega-3s (i.e., ALA).
The very small amount of omega-3 ALA found in most Americans’ diets comes from
seed oils like soy and canola, which contain far higher levels of omega-6 fatty acids.
The best common food sources of dietary ALA are green leafy vegetables (e.g., spinach,
kale, lettuces). Flaxseed, flax oil, hemp seeds, and hemp oil are the richest food sources
of ALA, and therefore constitute the best supplemental sources of ALA.
The human body converts from two to 15 percent of dietary ALA into DHA and EPA.
Nonetheless, people can survive and thrive if they consume enough plant-derived ALA.
In contrast people can survive and thrive entirely without ALA if they consume fish or fish
oil supplements, which are naturally rich in DHA and EPA.
Omega-6 EFAs
Linoleic acid (LA) is a short-chain omega-6 fatty acid that the body uses to make
arachidonic acid (AA), a long-chain omega-6 fatty acid which, like omega-3 DHA, is an
essential constituent of our cell membranes.
Most dietary LA comes from grains, seeds, and vegetables, while meats such as
chicken, beef, pork, and lamb contain both LA and AA.
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What do EFAs do in the body?
Essential fatty acids play key structural and functional roles in cell membranes, affecting
their fluidity, flexibility, permeability and the activity of critical membrane-bound enzymes.
DHA is selectively incorporated into cell membranes in the retina of the eye and into
postsynaptic neuronal cell membranes, which suggests it plays important roles in vision
and nervous system function.
Omega-6 and omega-3 EFAs also affect the expression of a number of genes, including
those involved with fatty acid metabolism and inflammation. They do this by interacting
with cellular compounds called “transcription factors”, including Nf-kappa-b, AP-1,
peroxisome proliferator-activated receptors (PPARs), and liver X receptors (LXRs).
Omega-3 and omega-6 EFAs also influence the production of ephemeral, hormone-like
compounds known as eicosanoids or autocoids, which include prostaglandins,
thromboxanes, and leukotrienes. These potent chemical messengers influence key body
functions, including blood pressure, blood clotting, inflammation, and immune function.
In response to injury, infection, or large amounts of dietary sugars, the body will initiate
an inflammatory response that begins when enzymes known as cyclooxygenases and
lipoxygenases act on omega-6 AA and omega-3 EPA in cell membranes to form
eicosanoids (prostaglandins, thromboxanes, and leukotrienes).
However, in contrast to the eicosanoids derived from EPA, which moderate
inflammation, eicosanoids derived from AA tend to induce strong, persistent
inflammation, blood vessel constriction, and coagulation.
The cell membranes of people who consume typical Western diets are excessively high
in omega-6 AA relative to the amount of omega-3 EPA. This imbalance results in the
preferential formation of pro-inflammatory eicosanoids derived from AA.
The chronic, low-level inflammation produced by diets high in omega-6 EFAs promotes
cardiovascular disease and cancer and is associated with Alzheimer’s disease.
Increasing one’s dietary intake of omega-3s increases the EPA content of your cell
membranes, resulting in higher proportions of eicosanoids that moderate inflammation.
Thanks to their specific effects on gene expression and eicosanoids, omega-3s tend to
decrease inflammation and the risk or severity of cardiovascular disease, diabetes,
autoimmune diseases, and certain cancers, while omega-6s tend to increase the risk
and severity of these conditions.
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Graphic courtesy www.fatsoflife.com
The extreme EFA imbalance in Western diets
Paleoanthropologists believe that, compared with modern diets, the diets of hominids
and early humans were much higher in omega-3s and much lower in omega-6s.
Constant exposure to this fatty acid intake ratio exerted a critical evolutionary influence
on the characteristics and nutritional requirements of present-day human bodies and
brains.
However, humans’ food consumption pattern began to change with advent of agriculture
(cereal grains like wheat) some 10,000 years ago, and these changes started to
accelerate rapidly in the mid-1800s as processed foods became widely available.
One of the most important human dietary changes brought about by agriculture and
processed foods was the shift away from foods relatively high omega-3s – leafy greens,
wild game, and pasture-grazed animals – in favor of foods high in omega-6 fatty acids,
such as seed oils, grains, and grain-fed livestock.
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This imbalance results in a very high proportion of omega-6 to omega-3 fats, relative to
the near-equal proportions that humans consumed throughout the vast majority of
evolutionary history.
This historically recent imbalance in EFA intake is extreme. While research indicates that
the body functions best when people consume two to four parts omega-6 EFAs to each
part omega-3 EFA, the average American’s diet contains from 10 to 40 times more
omega-6 EFAs than omega-3 EFAs.
The fact that most Americans and Europeans consume about 10 times more omega-6
fat in relation to omega-3s explains why government health authorities on both sides of
the Atlantic recommend that their citizens increase dietary intake of omega-3s.
(These authorities should, but rarely do, recommend that people also reduce their intake
of omega-6s.)
The enormous excess of omega-6s in the diets of developed countries accounts for the
beneficial effect seen in population surveys and controlled studies when people
consume less omega-6s and ample amounts of fish or supplemental omega-3s.
In other words, while most people in developed countries would benefit from increased
intake of omega-3s, experts believe that much benefit would also accrue from a sharp
decrease intake of omega-6s.
Because omega-6 EFAs are so abundant in the cooking oils, meats, poultry, and
processed or prepared foods that dominate most modern diets it is easier to redress the
imbalance by increasing omega-3 intake than by drastically reducing omega-6 intake.
Accordingly, it makes good sense to increase intake of both types of omega-3s – from
plants and fish – even though the plant form is less useful to the body. Small amounts of
short-chain omega-3s (ALA) are found in all leafy green plants, including dark cooking
greens such as spinach, collards, kale, and the like.
In addition, some brands of eggs are high in omega-3 DHA, thanks to chicken feed that’s
high in fish meal and/or plant sources of omega-3s. And some brands of yogurt, cereal,
waffles, and other packaged foods are fortified with omega-3 ALA, usually via addition of
flaxseed (or its oil), which is the seed highest in this fatty acid.
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Cardiovascular (Heart/Artery) Health
There is an overwhelming amount of scientific support for the idea that long-chain
marine omega-3s (EPA and DHA) provide cardiovascular benefits.
Health authorities in the US, UK, Europe, and Japan agree that people with higher than
average intakes of omega-3s enjoy significantly reduced risks of stroke and cardiac
death.
The American Heart Association recommends that people eat fish, particularly oily fish,
at least twice a week. For adults diagnosed with coronary heart disease, the Heart
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Association (AHA) recommends consuming one gram (1,000 mg) of omega-3 fatty acids
per day from fish and/or supplemental fish oil.
The AHA’s guidance is echoed by the U.S. Food and Drug Administration (FDA) and the
Agency for Healthcare Research and Quality (AHRQ), whose independent reviews of
the available evidence led both agencies to conclude that the long-chain “marine”
omega-3s from fish and fish oil (EPA and DHA) offer unique cardiovascular benefits not
available from the short-chain omega-3 fatty acid found in selected plant foods (alphalinolenic acid or ALA).
As the authors of the March, 2004 AHRQ review reported, “Overall, consumption of
omega-3 fatty acids, whether from fish or from supplements, reduces all-cause mortality
and improves various CVD outcomes. The evidence for benefit from ALA [i.e., plantderived omega-3] supplements is sparse and inconclusive.”
The FDA has permitted use of a qualified health claim on the labels of foods and dietary
supplements containing EPA and DHA:
“Supportive but not conclusive research shows that consumption of EPA and DHA
omega-3 fatty acids may reduce the risk of coronary heart disease.” (Note: The FDA
health claim cannot be used on foods or supplements containing only short-chain
omega-3s from plant foods such as flaxseed.)
Survivors of a heart attack who consume as little as one gram of omega-3s per day have
half the mortality from heart disease. Rates of heart disease are extremely low in Japan,
Iceland, and other countries where diets are very high in fish.
In addition, the results of recent evidence reviews indicate that marine omega-3s rival
the benefits of statin drugs when it comes to reducing the risk of heart attack, even
though omega-3s do not lower cholesterol levels substantially.
These findings support the increasingly influential hypothesis that one’s overall
cholesterol level may not be the most critical factor in the onset of cardiovascular
disease or the risk of heart attack. (People’s relative proportions of LDL and HDL
cholesterol seem more important than their total cholesterol levels.)
According to the most recent evidence review conducted by scientists affiliated with the
American Heart Association, marine omega-3s can decrease the risk of cardiovascular
disease and resulting heart attacks and strokes in several ways:





Prevent arrhythmias (irregular heartbeats) that can lead to sudden cardiac death.
(See our discussion of congestive heart failure and implanted cardiac
defibrillators, below.)
Decrease the risk of clotting (thrombosis) that can lead to a heart attack or
ischemic stroke. Ischemic strokes, which constitute three out of four strokes in
the US, result from insufficient blood flow to an area of the brain and typically
occur when an artery supplying the brain becomes constricted or blocked by a
clot.
Reduce blood levels of triglycerides (fats).
Slow the growth of arterial plaques.
Improve the function of the endothelial cells that line the arteries.
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

Lower blood pressure modestly.
Decrease inflammation in blood and artery walls.
Omega-3s in Congestive Heart Failure and Defibrillator Patients
Congestive heart failure (CHF) is the condition in which the heart is too weak to pump
blood effectively to the rest of the body.
CHF is characterized by reduced blood and oxygen supply to heart muscles, usually
caused by narrowing of coronary arteries from atherosclerosis (build up of sticky, fatty,
unstable “plaque” in artery walls): a condition called ischemic heart disease.
There is preliminary clinical evidence that omega-3s from fish oil can help reverse the
dangerous weight loss – called cardiac cachexia – that often occurs in advanced
congestive heart failure (CHF), and reduce blood levels of pro-inflammatory, cachexiapromoting immune-system chemicals (cytokines) found in CHF patients.
The results of some of the extant studies testing omega-3 supplements in people with
implanted cardioverter defibrillators (ICDs) have raised hypothetical concerns about
contraindications for omega-3s in patients with CHF and/or ICDs.
Some, but not all such studies detected a trend toward an increased risk of ventricular
arrhythmias – although not an increased risk of death – in patients taking fish oil.
People with CHF have dangerously few functional heart cells, which are starved for
blood flow, which makes them “hyper-excitable” and prone to trigger the arrhythmias that
cause most cases of sudden cardiac death.
Omega-3s selectively quiet hyper-excitable cells, bringing anti-arrhythmia benefits to
most heart patients … and to the many outwardly healthy people who die from
unexpected arrhythmias daily.
The hypothetical risk to people with congestive heart failure and/or implanted cardiac
defibrillators stems from the possibility that dietary omega-3s could suppress pumping
action in the hyper-excitable cells that account for an unusually large proportion of their
blood-pumping power.
However, this concern may be exaggerated, given the positive outcomes of other
studies that examined the effects of supplemental omega-3s in patients with ICDs.
In addition, the preponderance of research suggests that the ability of omega-3s to
reduce risk of sudden cardiac death extends to the four groups for which this
hypothetical concern has been expressed:




Patients with ischemic heart disease:
Patients with congestive heart failure.
Patients with implanted cardioverter defibrillators.
Patients who are susceptible to heart arrhythmias.
And, significantly – given the difficulty of verifying the reported diets of participants in
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arrhythmia effects associated with fish and fish oil have been confirmed in studies that
verified the level of omega-3 fatty acid intake by measuring plasma phospholipid fatty
acid content.
Omega-3s, inflammation and heart disease
The anti-inflammatory effects of omega-3s may play a greater role in heart health than
previously thought. In 2005, results from the ongoing ATTICA study in Athens, Greece
provided the first direct evidence showing that omega-3s reduce the kinds of
inflammation increasingly accepted as key risk factors for heart attack.
About 90 percent of the ATTICA study participants reported eating fish at least once a
month. Compared with those who ate little fish, the participants who ate the most fish –
about 10.5 ounces per week – had much lower levels of five key markers of
inflammation:





C-reactive protein (33 percent lower)
Interleukin-6 (33 percent lower)
Tumor necrosis factor-alpha (21 percent lower)
Serum amyloid A (28 percent lower)
White blood cells (4 percent lower).
The Greek researchers, who were careful to adjust for any other factors that might
reduce inflammation, also found significantly lower levels of these inflammation markers
in participants who ate between five and ten ounces of fish per week.
As the scientific team concluded, “Fish consumption was independently associated with
lower inflammatory markers levels, among healthy adults. The strength and consistency
of this finding has implications for public health and should be explored further.”
Lead author Antonis Zampelas, Ph.D., added that the results indicate that omega-3
supplements should be comparably beneficial: “… the amount of omega-3 fatty acids
seems to play a role in the reduction of inflammatory markers levels … omega-3 fatty
acid intake in the level of 0.6 grams [600 mg] per day could be [beneficial] to other
populations …”
American Heart Association Summary of Recommendations
for Omega-3 Fatty Acid Intake
Patients without documented coronary heart disease (CHD):
 Eat a variety of (preferably fatty) fish at least twice a week.
 Include oils and foods rich in alpha-linolenic acid (flaxseed, canola and soybean
oils; flaxseed and walnuts).
Patients with documented CHD:
 Consume about 1 g of EPA+DHA per day, preferably from fatty fish. EPA+DHA
supplements could be considered in consultation with the physician.
Patients who need to lower triglycerides:
 2 to 4 grams of EPA+DHA per day provided as capsules under a physician’s
care.
Patients taking more than 3 grams of omega-3 fatty acids from supplements should do
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so only under a physician’s care. High intakes could cause excessive bleeding in some
people.
Evidence from prospective secondary prevention studies suggests that taking EPA+DHA
ranging from 0.5 to 1.8 grams per day (either as fatty fish or supplements) significantly
reduces deaths from heart disease and all causes. For alpha-linolenic acid, a total
intake of 1.5–3 grams per day seems beneficial.
Increasing omega-3 fatty acid intake through foods is preferable. However, coronary
artery disease patients may not be able to get enough omega-3 by diet alone. These
people may want to talk to their doctor about taking a supplement. Supplements also
could help people with high triglycerides, who need even larger doses. The availability
of high-quality omega-3 fatty acid supplements, free of contaminants, is an important
prerequisite to their use.
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Alzheimer’s Disease and other Dementias
The results of a number of large studies suggest that people who consume fish once per
week or more enjoy a substantially reduced risk of Alzheimer's disease, compared with
those who rarely or never eat fish, and that people whose blood is high in DHA enjoy
significantly reduced rates of Alzheimer’s disease and other forms of dementia.
The mechanism by which omega-3s might reduce these risks is suggested by new
research from the Massachusetts Institute of Technology, where researchers found that
omega-3s increase the growth of synaptical connections between the brain cells of
rodents.
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Mental Health and Performance
In recent years, the results of population, clinical, and laboratory studies have
demonstrated a range of likely positive mental health and performance effects
associated with increased intake of omega-3s:
Substantial Evidence of Benefit
 Reduce the risk and severity of depression.
 Enhance mood and brain speed in healthy people.
 Extend periods of remission in bi-polar disorder.
 Reduce anger and hostility in alcoholics, cocaine addicts, troubled adolescents,
and violence-prone prisoners.
Preliminary, Mixed or Weak Evidence of Benefit
 Reduce the risk and severity of post-partum depression.
 Enhance conventional medical treatment of schizophrenia.
 Reduce the risk and severity of social anxiety disorder.
 Reduce frequency and severity of seizures in epileptics.
Omega-3s for Depression and Mood Disorders
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Among all mental conditions studied, the strongest evidence of benefit from higher
intake of omega-3s relates to prevention of depression and other mood disorders.
The authors of a recent evidence review (Freeman MP et al 2006) concluded that the
preponderance of evidence from two sources -- epidemiologic (population/diet) studies
and from studies comparing people’s tissue levels of marine omega-3s (EPA and DHA)
with their mental health status (“compositional” studies) -- indicate that higher intake of
omega-3s reduces the risk of depression.
These authors – who included leading psychiatric clinicians and researchers at
America’s National Institutes of Health -- noted that prior meta-analyses of randomized
controlled trials demonstrate that omega-3s produce statistically significant benefits in
regular (unipolar) and bipolar depression.
However, the authors of another review, published simultaneously (Appleton KM et al
2006), found the evidence from clinical trials too weak to support a firm conclusion. But
compared with the relative abundance of evidence from epidemiologic studies, there is
much less evidence available from clinical trials, and the results are difficult to pool for
analysis due to differences in the doses and specific omega-3s (DHA, EPA, or both)
used.
The authors of a third review of the available evidence, published the same year
(Sontrop J, Campbell MK 2006), made these relevant comments:
“The relationship between omega-3s and depression is biologically plausible and is
consistent across study designs, study groups, and diverse populations, which increases
the likelihood of a causal relationship.”
“It remains unclear whether omega-3 supplementation is effective independently of
antidepressant treatment, for depressed patients in general, or only those with
abnormally low concentrations of … [omega-3s].”
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Child Development
Because DHA forms an integral part of cell membranes in the brain and in the retina of
the eye it is considered important to optimal child development.
This hypothesis is borne out by the generally positive results of studies designed to
examine the effects of increased omega-3 intake by mothers and infants on mental and
vision development.
Specifically, the majority of studies suggest that increased omega-3 intake by mothers
and infants can enhance growing children’s intelligence, attention, hand-eye
coordination, and even their risk of developing high blood pressure in adulthood.
The last trimester of pregnancy is a critical period for the accumulation of DHA in the
brain and retina, so preterm infants are particularly prone to suffer the adverse effects of
insufficient DHA. Human milk contains DHA in addition to EPA and the plant-derived
omega-3 ALA. Still, until recently, ALA was the only omega-3 fatty acid added to
conventional infant formulas.
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Although preterm infants can synthesize DHA from ALA, they generally cannot make
enough to prevent declines in blood and cellular DHA concentrations. Accordingly,
preterm infant formulas typically contain added DHA.
Infant formulas enriched with DHA are also commercially available for full-term infants,
although the results of randomized controlled trials of these formulas on visual acuity
and development in term infants have, like those conducted in preterm infants, have
been mixed.
Since DHA appears to be critical to visual and neurological development, most expert
observers consider it prudent to give non-breastfed infants formula enriched with DHA to
ensure optimal visual and neurological development.
Mothers are the sole source of omega-3s for fetuses and exclusively breast-fed infants,
and preliminary findings suggest that mothers who take supplemental omega-3s may
reduce their risk of premature delivery and increase their length of gestation significantly.
Fish Intake by Pregnant or Nursing Mothers
A series of evidence reviews conducted in recent years indicate that the rewards of
eating fish during pregnancy and nursing outweigh any mercury-related risks to fetuses
and infants.
For example, analysis of data from a study of almost 9,000 British families found “… no
evidence to lend support to the warnings of the US [fish-and-mercury] advisory that
pregnant women should limit their seafood consumption”, and reported that “… children
of mothers who ate small amounts of seafood were more likely to have suboptimum
neuron-developmental outcomes than children of mothers who ate more seafood.”
(Hibbeln JR et al 2007)
The findings of five Harvard-led dietary fish risk/reward analyses found that fears among
the general public created by government mercury warnings directed to
expectant/nursing mothers may cause many other women – and many men – to cut fish
intake.
These were the Harvard teams’ basic findings:


Government advisories warning women of childbearing age about mercury
exposure appear likely to lead the general public to cut fish consumption, with a
resulting loss of substantial omega-3-related preventive health benefits”
If pregnant women decrease their fish consumption by 17 percent – as they did
in response to the government’s 2001 mercury advisory – the loss of omega-3
fatty acids during pregnancy would cut the nutritional benefit to infants of eating
fish by 80 percent. (In other words, that 17 percent reduction in fish intake had
an impact on their infants far greater than one would expect.)
In the best study of its kind, US researchers found no evidence of harm in children in the
Seychelles Islands, where mothers and children eat more than 10 times as much fish as
Americans. (On average, the ocean species the islanders consume contain the same
amounts of mercury as the species most commonly consumed in the US.) University of
Rochester researchers followed more than 600 children from birth through age 15,
finding no evidence of harm, and the study continues.
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In 2007, a group of 14 professors of obstetrics and nutrition (the Maternal Nutrition
Group) examined the evidence and urged women to eat at least 12 ounces of fish per
day.
This conclusion was based in part on the results of a study conducted in 2007 at the
Medical University of South Carolina (MUSC), which indicate that awareness of the
FDA/EPA fish-intake advisory for pregnant and nursing women caused 56 percent of
pregnant women to lower their fish consumption to levels well below the beneficial
minimums.
Pregnant and nursing women should favor the species lowest in mercury and highest in
omega-3s (e.g., Sardines, Sablefish, wild Salmon, low-weight, troll caught Tuna), or take
supplemental fish oil. They are advised to avoid four species that are high in mercury:
swordfish, shark, king mackerel, and tilefish.
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Attention-Deficit Disorders and Social/Cognitive Development
A growing body of evidence – including landmark results of a series of findings from the
Oxford-Durham project in England – indicates that increased intake of fish or
supplemental omega-3s can alleviate the symptoms of attention-deficit and
developmental coordination disorders.
And, intriguingly, there is recent evidence that a shift in the fat composition of the diets of
“normal” school-aged children – toward fish fats and away from animal and plant fats –
may enhance their psychosocial and cognitive functioning; i.e., their interactions with
others and their thinking capacity and speed.
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Cancer
The evidence that marine omega-3s can slow cancer growth substantially – and that
high intake of omega-6 EFAs promotes cancer growth substantially – is growing fast.
It includes epidemiological studies – in which researchers seek statistical correlations
between diet and cancer rates – as well as basic research in human and animal cancer
cells (in vitro studies) and animal studies (in vivo studies).
Likely explanations for the anti-cancer impact of dietary omega-3s include damping of
inflammation (a cause and growth promoter of common cancers), increased propensity
of cancer cells to commit “suicide” (via apoptosis or necrosis), and modulation of
estrogen signaling with regard to breast cancer.
When added to breast, prostate, and colon cancer cell lines cultured outside the body,
omega-3s inhibit reproduction or multiplication of cancer cells (i.e., “proliferation”); and
promote apoptosis (programmed cell death), and inhibit proliferation in human colorectal
mucosa.
The results of animal studies indicate that omega-3s decrease the occurrence and
progression of breast, prostate, and intestinal tumors.
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In the few human epidemiologic (case-control and cohort) studies where fish
consumption among subjects was relatively high, researchers have found significant
inverse relationships between fish or omega-3 intake and the risk of breast, prostate, or
colorectal cancer, and several types of cancer affecting white blood cells, including
leukemia, multiple myeloma, and non-Hodgkin lymphoma. In particular, EPA promotes
apoptosis in lymphoma cells in which the enzyme acyl-CoA synthetase (ACS) is
expressed to high degree.
Interestingly, people whose jobs require the handling of fish appear to enjoy a reduced
risk of leukemia and lymphoma, while people in occupations associated with beef cattle
– whose fat is high in omega-6 EFAs – suffer an increased risk for developing leukemia
and lymphoma.
Studies that measure tissue concentrations of EPA and DHA and dietary omega-6 to
omega-3 fatty acid ratios – as opposed to dietary intake of fish – would provide better
guidance regarding omega-3 intake and human cancer risk.
A large body of literature (of varying quality) suggests that omega-3 dietary enrichment
may help inhibit or prevent tumor growth.
In January of 2006, the U.S. Agency for Healthcare Research and Quality (AHRQ)
issued their review of the evidence, which included four conservative conclusions:
 “In a large body of literature spanning many countries and cohorts with different
demographic characteristics, the evidence does not suggest a significant
association between omega-3 fatty acids and cancer incidence.
 “In a small body of literature, there is no significant association between omega-3
fatty acids and clinical outcomes after tumor surgery.
 “Although the combination of omega-3 fatty acids, arginine, and RNA are
associated with a reduced risk of postoperative complications and reduced length
of hospital stay, it is not possible to ascertain whether these effects are due to
omega-3 fatty acids, arginine, RNA, or a combination of these.
 “A large body of literature (of varying quality) suggests that omega-3 dietary
enrichment may help inhibit or prevent tumor growth in some animal models; the
quality of the review articles is not, however, sufficient to permit drawing strong
conclusions.”
Adjunct cancer therapy
Evidence from animal studies indicates that supplemental omega-3s can improve the
efficacy of toxic cancer drugs such as doxorubicin, epirubicin, CPT-11, 5-fluorouracil, as
well as the efficacy of tamoxifen and radiation therapy. And preliminary clinical research
results indicate that omega-3 fatty acids can constitute a meaningful, if not equivalent,
alternative therapy for the small minority of patients unable to withstand radiation or
chemotherapy.
Omega-3s also appear to improve quality of life for people with cancer, in part by
combating cancer-associated appetite loss, physical wasting, and malnutrition. However,
the evidence is mixed.
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Diabetes
People who eat a lot of fish – like the Japanese, Icelanders, and Greenland’s Inuit
Eskimos – enjoy lower rates of diabetes. While there is no proof that diets high in fish or
marine omega-3s can prevent or treat diabetes, there is ample evidence that diets high
in fish or supplemental omega-3s can improve key cardiovascular functions and reduce
key risk factors for heart disease.
Heart disease is one of the most threatening “side effects” of diabetes, and this is why
the ADA recommends two to three servings of fish per week – advice that echoes similar
guidelines published by the American Heart Association. Eating fish frequently appears
to be safe and beneficial for diabetics, and some studies indicate that dietary fish may
protect against the development of impaired glucose tolerance – an early warning sign of
diabetes.
There is some evidence that fish oil or supplemental omega-3s (specifically, the EPA
found only in fish oil) may help prevent some of the adverse effects of diabetes, from
oxidation, inflammation, and hypertension to kidney, nerve, and blood-vessel damage.
For example, the authors of two relevant studies on the effects of marine omega-3s
(EPA and DHA) in diabetes came to these conclusions:


“… [omega-3 EPA] has significant beneficial effects on diabetic neuropathy and
serum lipids as well as other diabetic complications such as nephropathy and
macroangiopathy.”
“Supplementation with omega-3 fatty acids has beneficial effects on serum
[blood] triglycerides, HDL-cholesterol, lipid peroxidation and antioxidant
enzymes, which may lead to decreased rate of occurrence of vascular
complications in diabetes.”
NOTE: Supplemental omega-3s do not appear to increase insulin sensitivity, and have
worsened diabetics’ blood sugar control initially in some, but not all studies. This effect
seems to be a temporary, self-correcting phenomenon, but diabetics should monitor their
blood sugar closely when first taking omega-3 supplements.
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Inflammatory Diseases (rheumatoid arthritis, IBS/Crohn’s, asthma, etc.)
Autoimmune diseases such as type 1 diabetes, lupus and rheumatoid arthritis have long
defied attempts to explain why the immune system stops regulating itself and begins
attacking the body’s own tissues, with inflammation serving as a primary self-damaging
weapon.
Early in 2007, a team of scientists from the Whitehead Institute and the Dana Farber
Cancer Institute identified a key gene regulator called Foxp3. When it goes awry, the
body no longer makes working versions of regulatory T cells – the cells that normally
keep the body’s immune system in check. This finding may hasten efforts to find
effective new therapies for autoimmune diseases.
The effect of fish oil on the various inflammatory auto-immune disorders depends on the
specific mechanisms of the disorder as well as the dose and duration of supplemental
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15
omega-3s. Outcomes also depend on the balance between omega-3 and omega-6 fatty
acids, the relative proportion of EPA and DHA, and dietary intake of vitamin E, which can
counter the anti-inflammatory effects of omega-3s.
Fish oil is only mildly effective in damping acute, extreme inflammation. Some animal
studies show success in acute inflammation, but these used very high doses that may
be unsustainable for humans.
In chronic inflammatory disorders where fish oil has shown benefit, it took several weeks
for positive results to appear. Still, the mild anti-inflammatory effects of supplemental
omega-3s – likely related to reduced production of pro-inflammatory cytokines – has
lead to substantial improvement of symptoms in some seriously ill patients.
Research indicates that fish oil supplementation seems especially effective in disorders
involving inappropriate activation of the immune system. Fish oil has only a mild effect
on the episodes of extreme inflammation that occur periodically in diseases such as
rheumatoid arthritis, SLE (lupus) and Crohn's disease, but some studies indicate that
fish oil could prevent relapses.
In diseases where the inflammation is mild, such as IgA nephropathy, studies show that
fish oil may slow or even prevent progression of the disease.
High intakes levels of long-chain omega-3s from fish oil inhibits a wide range of immune
functions implicated in certain auto-immune disorders. These include antigen
presentation, expression of adhesion molecules, Th1 and Th2 responses, production of
pro-inflammatory cytokines and eicosanoids, and promoting apoptosis (suicide) among
lymphocytes (white blood cells of the immune system).
Interestingly, vitamin E exerts critical influences over the interactions of long-chain
omega-3s with immune functions, often reversing the effects of fish oil. Thus, it may be
counterproductive to take supplemental vitamin E with fish oil when treating
inflammatory conditions.
Animal experiments indicate that omega-6 and omega-3 fatty acids display varying
effects in two classes of auto-immune disease:



Auto-antibody-mediated diseases: Diets low in fat, deficient in essential fatty
acids, or high in omega-3s from fish oil increase survival and reduce disease
severity. Diets high in fat and omega-6 LA increase disease severity.
T cell-mediated diseases: Diets deficient in essential fatty acids or supplemented
with in omega-3s from fish oil promote disease, whereas diets high in omega-6
LA prevent these or reduce their severity.
T cell- and antibody-mediated autoimmune disease: Metabolites of omega-6 LA
are protective.
Both types of long-chain polyunsaturated fatty acids – omega-6 and omega-3 – can be
helpful in treating human autoimmune-inflammatory disorders, but the precise
mechanisms by which these fatty acids exert their clinical effects are not well
understood. The view that all omega-6 fatty acids are pro-inflammatory is inaccurate, in
part, and their essential regulatory role in the immune system is more important than
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16
often appreciated. The issue is that the American diet contains an overabundance of
omega-6 fatty acids, largely from vegetable oils and grain-fed meat and poultry.
Omega-3 EFAs have been tested, with mixed results, in diseases characterized by
chronic inflammation, such as rheumatoid arthritis (RA), inflammatory bowel and Crohn’s
disease, psoriasis, eczema, hay fever, and asthma.
Rheumatoid arthritis: The results of several controlled clinical trials indicate that
supplemental fish oil decreases joint tenderness and reduces the requirement for antiinflammatory medication in rheumatoid arthritis patients. The available laboratory
evidence indicates that omega-3s reduce the inflammation characteristic of RA, which
causes pain and damage to joint tissues, and that EPA may be more important than
DHA in reducing inflammatory markers of the disease.
Inflammatory bowel disease: While clinical trials of omega-3s have not produced
significant alleviation of symptoms, some Crohn’s disease patients taking fish oil
supplements have remained in remission longer than those taking placebo pills.
Asthma: Omega-3 supplements have decreased the production of inflammatory
chemicals in asthmatic patients, and there is some evidence that children of mothers
with higher omega-3 intake, and children with higher tissue levels of omega-3s, enjoy a
reduced risk of asthma.
There is also some clinical evidence that omega-3s can alleviate symptoms. However,
two systematic reviews of randomized controlled trials of long-chain omega-3 fatty acid
supplementation in asthmatic adults and children found that while omega-3 supplements
can positive effects of on pulmonary function tests, asthmatic symptoms, medication
use, and bronchial hyper-reactivity, these results are not consistent across all studies.
Psoriasis and Eczema: The results of clinical studies testing the effects of omega-3s in
patients with psoriasis or eczema preclude unambiguously positive conclusions. As the
authors of a recent review put it, “… the results of studies evaluating the therapeutic
benefit of dietary fish oil have been conflicting and not clearly dose-dependent.”
Trials in which people took fish oil capsules produced mixed, generally minor benefits.
But the results were far better in trials that involved intravenous omega-3s. While these
highly positive results exhibit the strong anti-inflammatory effects of high doses of
omega-3s, it is not very practical or cost-effective for patients to get them this way on an
ongoing basis.
The results of a crossover clinical trial in which patients alternated eating oily fish or
white fish showed that the oily fish produced modest improvements. These results
suggest that substances in oily fish or undistilled fish oils (probably phospholipids) may
enhance the efficacy of omega-3s, compared with the isolated omega-3s used in
virtually all trials.
The reasons why supplemental omega-3s exhibit mixed results may relate to the
differences among inflammatory auto-immune disorders, in terms of the precise parts of
the immune system affected.
In addition, the results of animal studies indicate that the effect of dietary fatty acids on
autoimmune diseases depends on both the type of autoimmune disorder and the
amounts and relative proportions of fatty acids consumed.
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17
Seizure disorders
The positive results of most of several animal studies, and of a small clinical trial, offer
preliminary evidence that increased omega-3 intake may reduce the frequency and
strength of epileptic seizures.
It is believed that omega-3s may yield these benefits by the same mechanism of some
anti-seizure drugs, which reduce the “excitability” of cell membranes in the brain’s
hippocampus region. This mechanism is similar to the one through which dietary omega3s are proven to reduce the risk of cardiac arrhythmias.
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Safety Considerations
While omega-3s are proven to protect against heart attacks and strokes, they may be
inadvisable in certain circumstances. The American Heart Association offers this
guidance: “Patients taking more than 3 grams of omega-3 fatty acids from supplements
should do so only under a physician’s care. High intakes could cause excessive
bleeding in some people.”
However, doses as high as 8 grams of omega 3 fatty acids per day (contained in from 10
grams to 27 grams of fish oil) show virtually no significant adverse effects.
As the author of a recent review notes, “It has been suggested that the potential antithrombosis [anti-clotting] effect of fish oils may theoretically increase the risk for
bleeding, which may be a safety concern for individual patients. However, clinical trial
evidence has not supported increased bleeding with omega-3 fatty acid intake, even
when combined with other agents that might also increase bleeding (such as aspirin and
warfarin).” (Bays HE 2007)
The most common side effects from fish oil consumption are complaints of fish-flavored
burps, which can be reduced by taking the capsules in the middle of a meal, and by
taking lemon-flavored oil. As with other dietary oils, gastrointestinal complaints including
loose stools have been reported from people taking relatively high doses, albeit rarely.
Check with your doctor before taking omega-3 fish oil supplements if you meet any of
these criteria:



Taking blood-thinning drugs, including warfarin (coumadin) or aspirin, ibuprofen
(Advil), naproxen (Aleve), and other anti-inflammatory pain relievers, including
COX-2 inhibitors (e.g., Vioxx, Celebrex). There has never been a reported case
of clinical bleeding attributed to fish oil consumption, even during surgery, but
people with bleeding disorders and those taking blood thinners or anticoagulants
should consult their physician before taking omega-3 supplements.
Diagnosed with a serious cardiovascular condition – especially a diagnosis of
angina or an irregular heartbeat that involves use of an implantable cardioverter
defibrillator (ICD). While omega-3s generally reduce the risk of arrhythmias, they
may raise the risk of arrhythmias in people with ICDs.
Diagnosed with type II diabetes. Omega-3 supplements appear to improve the
health prospects of type II diabetics, but they can worsen blood sugar control
temporarily in diabetics who have never taken them. This effect usually fades
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18
within a few days or weeks. Type II diabetics who have never taken omega-3
supplements should start with a relatively low dose (e.g., 150 mg per day) and
increase it gradually to the amounts indicated under “Intake Recommendations”,
below.
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Intake Recommendations
The American Heart Association recommends that people eat fish, particularly oily fish,
at least twice a week, and that adults diagnosed with coronary heart disease consume
one gram (1,000 mg) of omega-3 fatty acids per day from fish and/or supplemental fish
oil.
However, this leaves open the question of daily intake recommendations for healthy
people. It seems sensible to consider following the intake recommendations of the two
scientific bodies with the greatest expertise in this area: the US Institute of Medicine
(IOM) and the International Society for the Study of Fatty Acids and Lipids (ISSFAL).


ISSFAL recommends that adults consume 660 mg of omega-3s per day.
IOM recommends that men consume 400 mg of omega-3s per day, and that
women consume 260 mg per day.
Each 1000 mg capsule of Vital Choice Sockeye Salmon Oil provides about 160 mg of
the two key omega-3s (90 mg EPA and 70 mg DHA), so you would need to take two to
four capsules per day to meet the IOM and ISSFAL guidelines, as follows.
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
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
To meet ISSFAL’s optimal daily intake level (660 mg), MEN and WOMEN should
take four capsules of our sockeye oil per day.
To meet the IOM’s adequate daily intake level (400 mg), MEN should take three
capsules of our sockeye oil per day.
To meet the IOM’s adequate daily intake level (260 mg), WOMEN should take
two capsules of our sockeye oil per day.
To meet the American Heart Association recommendation for adults diagnosed
with coronary heart disease (1,000 mg), MEN and WOMEN should take six to
seven capsules of our sockeye oil per day.
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www.vitalchoice.com
19
Best Omega-3 Sources*
Wild Salmon
Sardines
Cold water Tuna (e.g., Pacific albacore)
Sablefish
Herring
Mackerel
Pacific Oysters and Scallops
Sources to Avoid
Shark*
Swordfish*
King Mackerel*
Tilefish*
Farmed Salmon***
*Minimal content of mercury and other contaminants; sustainably harvested
**Relatively high in mercury
***Farmed Salmon are high in omega-3s, but are also high in competing omega-6 fatty
acids and tend to be high in persistent organic pollutants (PCBs, dioxins)
Further Reading
“Vital Choices” Newsletter Archive: http://www.vitalchoice.com/newsletter_index.cfm
(Enter a term related to your interest, such as “diabetes”, in the Search box on the
archive page.)
VitalChoice.com Health Benefits page: http://www.vitalchoice.com/health.cfm
National Institutes of Health -- Essential Fatty Acid information at
http://efaeducation.nih.gov
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Essential fatty acids (EFAs) in brief
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